Fragile X syndrome (FXS) is the most commonly known genetic disorder associated with autism spectrum disorder (ASD), with 4% to 5% of individuals with a diagnosis of ASD having comorbid FXS. Approximately 25% to 30% of individuals with FXS also have a diagnosis of autism (AUT) while an additional 50% to 90% display core features associated with the symptomatology of ASD. These features include gaze aversion, communication deficits, and social withdrawal. However, controversy exists as to the nature of the underlying deficits in social/emotional processes in FXS versus idiopathic AUT. Although the association between FXS and ASD has been well documented at the behavioral level, the underlying neural mechanisms associated with the social/emotional deficits in these groups remain unclear. It has been proposed that while FXS and AUT differ on the single-gene level, they may share common perturbations in neural network development and maintenance, dependent on complex cascading network mechanisms at the genetic, epigenetic and environmental level. It is the aim of this proposal to investigate the commonalities and differences in underlying central circuitry of social and emotional processes in FXS and idiopathic AUT and relate these to behavioral measures such as gaze fixation and the domain and severity of AUT characteristics expressed at an individual level using fMRI measures during a facial-fear processing task. This proposal is designed to test the hypothesis that social impairments in individuals with FXS are associated with differences/deficits in brain activation patterns to social/emotional stimuli and that these activation patterns are dependent on behavioral domain and severity of AUT characteristics within FXS individuals. Furthermore, it is predicted that aberrant cortical and sub-cortical connectivity in emotional face processing networks impedes and impairs information processing from perception to response in FXS and that this dysconnectivity is also associated with severity of AUT characteristics in FXS individuals. Finally, possible underlying differences in brain morphometry, both between FXS and AUT, and TD groups, as well as the relationship between brain structure and function and domain and severity of AUT characteristics within FXS individuals will be investigated. how autism characteristics in individuals with fragile X syndrome may be related to differences in how their brain processes social and emotional inputs, such as reading emotion from another person's face. [unreadable] [unreadable] [unreadable]